PMID- 18083903
OWN - NLM
STAT- MEDLINE
DCOM- 20080331
LR  - 20200930
IS  - 0363-6135 (Print)
IS  - 0363-6135 (Linking)
VI  - 294
IP  - 2
DP  - 2008 Feb
TI  - Prevention of HIF-1 activation and iNOS gene targeting by low-dose cadmium 
      results in loss of myocardial hypoxic preconditioning in the rat.
PG  - H901-8
AB  - This study aimed to underline the interaction between hypoxia-inducible factor-1 
      (HIF-1) and the inducible nitric oxide synthase (iNOS) gene in vivo and their 
      contribution to the delayed myocardial preconditioning induced by acute 
      intermittent hypoxia (IH) in the rat using chromatin immunoprecipitation and 
      pharmacological inhibition by low-dose cadmium. Langendorff-perfused hearts of 
      Wistar rats exposed to normoxia or IH 24 h earlier were submitted to global 
      ischemia and reperfusion. Effects of iNOS inhibition by aminoguanidine (100 
      microM) before ischemia or of low-dose injection of cadmium chloride (1 mg/kg) 
      before normoxia or IH were tested. Myocardial HIF-1 and iNOS quantification and 
      in vivo chromatin immunoprecipitation of HIF-1 bound to the iNOS gene promoter 
      were performed. IH-induced delayed cardioprotection resulted in an improvement in 
      coronary flow and functional recovery at reperfusion and a decrease in infarct 
      size. Myocardial HIF-1 activity was increased with resulting targeting of the 
      iNOS gene. Aminoguanidine abolished the cardioprotective effects of IH. Cadmium 
      chloride treatment before IH prevented myocardial HIF-1 activation (72.3 +/- 4.0 
      vs. 42.1 +/- 9.7 arbitrary units after cadmium chloride; P < 0.05), targeting of 
      the iNOS gene, iNOS expression, and preconditioning (infarct size: 15.9 +/- 5.6 
      vs. 30.1 +/- 5.4% after cadmium chloride; P < 0.05). This study is the first to 
      demonstrate the interaction of HIF-1 with the myocardial iNOS gene in situ after 
      hypoxic preconditioning. Prevention of HIF-1 activation and iNOS gene targeting 
      by a single low dose of cadmium abolished the delayed cardioprotective effects, 
      bringing insight into the cardiovascular consequences of cadmium exposure.
FAU - Belaidi, Elise
AU  - Belaidi E
AD  - Laboratoire HP2, Hypoxie et Physiopathologies Cardiovasculaire et Respiratoire, 
      Institut National de la Sante et de la Recherche Medicale ERI17, Grenoble, 
      France.
FAU - Beguin, Pauline C
AU  - Beguin PC
FAU - Levy, Patrick
AU  - Levy P
FAU - Ribuot, Christophe
AU  - Ribuot C
FAU - Godin-Ribuot, Diane
AU  - Godin-Ribuot D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20071214
PL  - United States
TA  - Am J Physiol Heart Circ Physiol
JT  - American journal of physiology. Heart and circulatory physiology
JID - 100901228
RN  - 0 (Chromatin)
RN  - 0 (Guanidines)
RN  - 0 (Hif1a protein, rat)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - J6K4F9V3BA (Cadmium Chloride)
RN  - SCQ4EZQ113 (pimagedine)
SB  - IM
MH  - Animals
MH  - Biotransformation/physiology
MH  - Blotting, Western
MH  - Cadmium Chloride/*toxicity
MH  - Chromatin/metabolism
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Guanidines/pharmacology
MH  - Hypoxia
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*antagonists & inhibitors
MH  - Immunoprecipitation
MH  - *Ischemic Preconditioning, Myocardial
MH  - Male
MH  - Myocardial Reperfusion Injury/physiopathology
MH  - Nitric Oxide Synthase Type II/*genetics
MH  - Rats
MH  - Rats, Wistar
EDAT- 2007/12/18 09:00
MHDA- 2008/04/01 09:00
CRDT- 2007/12/18 09:00
PHST- 2007/12/18 09:00 [pubmed]
PHST- 2008/04/01 09:00 [medline]
PHST- 2007/12/18 09:00 [entrez]
AID - 00715.2007 [pii]
AID - 10.1152/ajpheart.00715.2007 [doi]
PST - ppublish
SO  - Am J Physiol Heart Circ Physiol. 2008 Feb;294(2):H901-8. doi: 
      10.1152/ajpheart.00715.2007. Epub 2007 Dec 14.